tbuckley/cabot-search huggingface dataset:
Anti PD-1 monoclonal antibody in patients with MSI-high and/or high tumor mutational burden for solid malignancies.
Authors: Veronica Guerra, Yasmin Alwash, Marisol Lilian Ocampo, Mike Cusnir
Journal: Journal of Clinical Oncology (2022)

e15539 Background: High microsatellite instability (MSI-H) tumors have been associated with good responses to check-point inhibitors (CPI). With overall response rates (ORR) ranging between 36-46% among colorectal cancer (CRC) and other solid malignancies. Data regarding predictors of response and responses in non-CRC malignancies remains limited. We sought to evaluate the response to PD-1/PDL-1 CPI in patients with MSI-H and/or high TMB solid malignancies. Methods: Retrospective analysis of 16 patients (pts) who received 18 CPI-based therapies between October 2017 and February 2022. MSI-H and TMB status was assessed by CARIS, Guardant360 or INVITAE genetic testing. Primary objective was to determine objective response rate (ORR), defined as complete response (CR) or partial response (PR) by RECIST1.1. Secondary outcomes included progression-free survival(PFS); overall survival (OS), and duration of overall response (DOR). Results: A total of 16 pts were included. The median age of 72 years (range 53-83), 44% were male and 75% Hispanic. 44% of pts had RCR and 50% were previously treated, and 50% were stage IV at diagnosis. The most common mutations were BRCA2 31%, PIK3cA 31%, KRAS 25%, and GNAS 25%. The majority of pts received single-agent CPI therapy (72%). After a median follow-up of 52 months, 11 pts continued to receive therapy, 2 pts completed treatment. 3 pts died from progression of the disease. 1 pts switched from single-agent pembrolizumab to nivolumab-ipilimumab combination followed by nivolumab maintenance due to disease progression. 15 pts were evaluable for response with an ORR of 33%, including 33% among pts with CRC and 27% for non-CRC malignancies. (Table - Response rates) The OS was not reached (NR), with a PFS of 53 months (PFS of 64% at 1 year and 56% at 4 years). The median DOR was not reached (NR). The treatment was well tolerated and pts received a median of cycles was 19 (range 3-51) with no discontinuations due to toxicities. The molecular mutations, clinical characteristics, type of malignancy, MSI-H, or H-TMB status were not significantly associated with response to CPI after logistical regression analysis. Conclusions: CPIs are an effective treatment option for patients with MSI-H and/or High TMB, with an ORR of 33%. However, pts achieved durable responses, with a median DOR not reached. We identify a higher incidence of SD rates among CRC pts (67% vs. 18% non-CRC). We did not identify any predictors associated with response to CPI, likely due to the small number of pts. However, there was a tendency to highest response rates among pts with MSI-H and high TMB.[Table: see text]
Non-myeloablative allogeneic blood or marrow transplantation (AlloBMT) with post-transplant cyclophosphamide (PTCy) for peripheral T-cell lymphoma (PTCL): Improved outcomes with peripheral blood (PB) allografts and increased total body irradiation (TBI) to 400 cGV.
Authors: Cole Harris Sterling, Michael Sang Hughes, Hua-Ling Tsai, Ephraim Joseph Fuchs, Kathryn Yarkony, Ravi Varadhan, Douglas Edward Gladstone, Lode J. Swinnen, Richard J. Jones, Nina D. Wagner-Johnston, Richard F. Ambinder
Journal: Journal of Clinical Oncology (2022)

7047 Background: The use of PTCy for graft-versus host-disease (GVHD) prophylaxis has revolutionized alloBMT, but there is limited published experience in PTCL. Methods: All patients with PTCL who received a non-myeloablative alloBMT using PTCy-based GVHD prophylaxis between January 2004 and December 2020 at Johns Hopkins Hospital were analyzed. Standard population statistics were used. Results: Sixty-five patients were identified. The median age was 59 years (range, 24-75 years). Lymphoma histology included PTCL-not otherwise specified (n=24), ALK-negative anaplastic large cell lymphoma (n=14), angioimmunoblastic T-cell lymphoma (n=7), enteropathy-associated T-cell lymphoma (n=6), hepatosplenic T-cell lymphoma (n=4), and other (n=10). Eleven patients were in first complete remission (CR1, 17%). The remaining patients were in first partial remission (PR1) or underwent salvage therapy to at least PR prior to transplant. Forty-eight patients received an alloBMT from a haploidentical related donor (74%), 10 from a fully matched donor (15%), and 7 from a mismatched unrelated donor (mMUD, 11%). All patients received non-myeloablative conditioning with fludarabine, cyclophosphamide, and TBI. The graft source was bone marrow (BM) in the first 46 patients (71%). Because of relatively high relapse rates, in 2018 we began using PB and increased TBI from 200 to 400 cGy; the remaining 19 patients (29%) received this regimen. GVHD prophylaxis was PTCy, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. With a median follow up of 2.8 years, the 3-year progression-free survival (PFS) for the entire cohort was 39% (95% confidence interval [CI] 28-54%), and the 3-year overall survival (OS) was 43% (95% CI 31-58%). The cumulative incidence (CuI) of relapse and non-relapse mortality (NRM) at 1 year was 25% (95% CI 14-35%) and 12% (95% CI 4-20%), respectively. Among 29 cases of GVHD (45%), 2 were grade 3-4 acute GVHD (3%) and 3 were severe chronic GVHD (5%). Univariate analysis including age, histology, mMUD, PB/400cGy, and CR1 revealed only PB/400 cGy TBI as a significant predictor of survival, relapse, or NRM. Outcomes by source. Conclusions: AlloBMT with non-myeloablative conditioning and PTCy is safe and well-tolerated in patients with PTCL. Our preliminary data suggest increasing TBI dose to 400 cGy and using PB allografts may offer improved disease control and better survival outcomes, though additional studies are needed to confirm these findings. [Table: see text]
Oncology hospital at home in rural communities: The Huntsman at Home rural experience.
Authors: Kathi Mooney, Kimberly Dumas, Angie Fausett, Marcene Littledike, Cornelia M Ulrich, Karen Titchener
Journal: Journal of Clinical Oncology (2022)

1535 Background: Oncology hospital at home programs have shown promise in decreasing unplanned health care utilization while improving quality of life. While most hospital at home programs serve local urban areas, we extended our oncology hospital at home program, Huntsman at Home, to provide equitable distribution of program services for cancer patients living in rural communities at a distance from our cancer center. Methods: Utilizing a community engagement approach we redesigned our urban Huntsman at Home program for 3 rural communities in Southeastern Utah, a 2 to 5 hour one-way drive from Huntsman Cancer Institute. We systematically collected patient data and program modifications required for rural community delivery during the program’s first 6 months. Care was delivered by on-ground and telehealth nurse practitioner visits and on-ground registered nurse and physical therapy visits. Cardiovascular remote monitoring was utilized during acute care episodes. Results: A total of 47 cancer patients (31 men; 16 women; mean age 69 years) were admitted to the rural program during the first 6 months. Seven patients had 9 acute illness episodes of care. The average length of acute episode care was 6.1 days for treatment of infection, respiratory distress/ hypoxia, cardiac instability (hypotension, tachycardia), and dehydration/electrolyte imbalance and uncontrolled vomiting. Forty patients received subacute management aimed to prevent acute episodes and escalation to the emergency department (ED) or hospitalization. Subacute patients were in the program an average of 15.8 days. There were 4 appropriate escalations (2 hospitalizations, 1 ED visit returned to home and 1 ED visit with hospitalization) for symptoms related to disease progression requiring imaging and hospital-based procedures and one for diagnosis of a post-surgical PE. We found geographic and social determinates of health impacted rural patients’ cancer burden, most notably transportation barriers (44.7%). Secondarily, we found food insecurity impacted nutritional status in 14.9% of patients. A significant number of patients experienced financial toxicity (29.8%) related to lost wages, co-pays and/or out of pocket expenses for care. Lack of health literacy impacted 48.9% of patients effectively navigating their health care and self-management at home. Robust communication and coordination between the hospital at home clinical team, local primary care providers, the rural hospital, community resources and the patients’ cancer center oncology team were keys to improving care pathways. Conclusions: Rural oncology hospital at home is feasible and addresses geographic disparities in equitable access to acute and subacute cancer care in local communities. It requires adaptation to rural needs and culture, coordinated escalation procedures and a focus on addressing geographic and social determinates of health that impact cancer burden.
Observer performance study to examine the feasibility of the AI-powered PD-L1 analyzer to assist pathologists’ assessment of PD-L1 expression using tumor proportion score in non–small cell lung cancer.
Authors: Seokhwi Kim, Hyojin Kim, Wonkyung Jung, Soo Ick Cho, Joel Bentz, Warren Clingan, Kevin Golden, Ramir Arcega, Hyunsik Bae, Dawn L. Butler, Sangjoon Choi, Maryam Farinola, Daniel Harrison, Soohyun Hwang, Minsun Jung, Nilesh Kashikar, Hyunsung Kim, Julia Manny, Carmen Winters, Jonathan H. Hughes
Journal: Journal of Clinical Oncology (2022)

8529 Background: Programmed death ligand 1 (PD-L1) expression is the standard biomarker for PD-L1 inhibitors in advanced non-small cell lung cancer (NSCLC). However, evaluation of PD-L1 tumor proportion score (TPS) by pathologists causes inter-observer variation and demands time to interpret. This study aimed to evaluate the benefit of the artificial intelligence (AI) algorithm in assisting pathologists to determine TPS on PD-L1 immunohistochemistry (IHC) whole-slide images (WSIs) in NSCLC. Methods: Lunit SCOPE PD-L1, an AI-powered PD-L1 TPS analyzer, was developed from 393,565 tumor cells annotated by board-certified pathologists for PD-L1 expression in 802 WSIs stained by 22C3 pharmDx IHC. The AI model was developed based on a region-based convolutional neural network, and the model can detect and count PD-L1 positive or negative tumor cells from WSIs to calculate TPS. Seven independent board-certified pathologists scored ground truth (GT) of PD-L1 TPS from 199 WSI of NSCLC stained by 22C3 pharmDx IHC. TPS from each GT reader was grouped as negative (&lt; 1%), low (1% to 49%), or high (≥ 50%). The GT of each slide was determined by the consensus of GT readers. Another twelve independent board-certified pathologists scored PD-L1 TPS from the same WSIs as observer performance testers (OPT). They scored TPS twice with a washout interval of 4 weeks, with or without AI assistance. TPS accuracy change and reading time of OPT reader according to the presence or absence of AI assistance were analyzed. Results: The standalone accuracy of the AI model was 0.809 (95% CI: 0.690–0.941). With AI assistance, the overall accuracy of TPS had been changed from 0.799 (95% confidence interval [CI]: 0.764–0.836) to 0.832 (95% CI: 0.796–0.869) (P = 0.004). AI assistance increased the accuracy rate in 11 out of 12 OPT readers. The result of the generalized linear mixed model revealed that AI assistance and specimen type affected the probability of correct answer, while the order of reading did not (Table). The mean time to read with AI was 195.4±506.5 (mean±standard deviation) seconds, which was significantly shorter than the mean time to read without AI (285.1±1578.4, P &lt;0.001). Conclusions: This study demonstrates that an AI-powered PD-L1 TPS analyzer can assist board-certified pathologists in evaluating TPS of NSCLC by improving the accuracy of TPS group evaluation and reducing the time to read slides.[Table: see text]
Prospective validation of a new imaging scorecard to assess leptomeningeal metastasis: A joint EORTC BTG and RANO effort.
Authors: Emilie Le Rhun, Patrick Devos, Sebastian Winklhofer, Hafida Lmalem, Dieta Brandsma, Priya Kumthekar, Marion Smits, Joerg Tonn, Kurt A. Jaeckle, Matthias Preusser, Michael J. Glantz, Patrick Y. Wen, Martin Bendszus, Michael Weller
Journal: Journal of Clinical Oncology (2022)

2026 Background: Validation of the 2016 RANO MRI scorecard for leptomeningeal metastasis failed for multiple reasons. Accordingly, this joint EORTC Brain Tumor Group and RANO effort sought to prospectively validate a revised MRI scorecard for response assessment in leptomeningeal metastasis. Methods: Coded paired cerebrospinal MRI of 20 patients with leptomeningeal metastases from solid cancers at baseline and follow-up after treatment and instructions for assessment were provided via the EORTC imaging platform. The Kappa coefficient was used to evaluate the inter-observer pairwise agreement. Results: Thirty-five raters participated, including 9 neuroradiologists, 17 neurologists, 4 radiation oncologists, 3 neurosurgeons and 2 medical oncologists. Among single leptomeningeal metastases-related imaging findings at baseline, the best median concordance was noted for hydrocephalus (Kappa = 0.63), and the worst median concordance for spinal linear enhancing disease (Kappa = 0.46). The median concordance of raters for the overall response assessment was moderate (Kappa = 0.44). Notably, the interobserver agreement for the presence of parenchymal brain metastases at baseline was fair (Kappa = 0.29) and virtually absent for their response to treatment. 394 of 700 ratings (20 patients x 35 raters, 56%) were fully completed. In 308 of 394 fully completed ratings (78%), the overall response assessment perfectly matched the summary interpretation of the single ratings as proposed in the scorecard instructions. Conclusions: This study confirms the principle utility of the new scorecard, but also indicates the need for training of MRI assessment with a dedicated reviewer panel in clinical trials. Electronic case report forms with “blocking options” may be required to enforce completeness and quality of scoring.
STOPTRAFFIC-1: A phase I/II trial of SX-682 in combination with nivolumab for refractory <i>RAS-</i>mutated microsatellite stable (MSS) metastatic colorectal cancer (mCRC).
Authors: Benny Johnson, Scott Kopetz, Hyunsoo Hwang, Ying Yuan, Ronald Anthony DePinho, John Zebala, Michael J. Overman
Journal: Journal of Clinical Oncology (2022)

TPS3638 Background: Refractory RAS mutated MSS mCRC represents a critical unmet need with minimal response to immune checkpoint blockade (ICB). Preclinical CRC models reveal that KRAS mutations activate the CXCR2 axis promoting an immunosuppressive tumor microenvironment (TME). This occurs via KRAS repression of interferon regulatory factor 2 (IRF2) resulting in upregulation of CXCL3 chemokines, which bind CXCR2 and recruit myeloid-derived suppressor cells (MDSC; Liao et al, Cancer Cell 2019; Grover et al, Cancer Discovery, 2022). SX-682 is a novel oral small-molecule inhibitor of the CXCR1/2 chemokine receptors involved in MDSC-recruitment to the TME. This proof-of-concept study investigates whether de novo immunotherapy resistance in MSS RAS mutated mCRC can be overcome by treatment with a small molecule CXCR1/2 antagonist in combination with anti-PD-1 therapy. Methods: STOPTRAFFIC-1 (NCT04599140, enrolling) is a phase I/II, open-label, dose-escalation/dose expansion study of SX-682 in combination with nivolumab to evaluate safety and clinical activity for patients (pts) with refractory RAS ( KRAS and NRAS) mutated MSS mCRC. Key eligibility criteria: patients (pts) with MSS mCRC with measurable disease, progression or intolerance to at least 2 prior lines of standard therapy, and ECOG 0 or 1. Pts will receive SX-682 (5 dose levels: 25 mg, 50 mg, 100mg, 200mg, or 400 mg by mouth twice daily) administered in an 8-week cycle with intravenous nivolumab (480 mg) on days 1 and 29 of each cycle. Adverse events are assessed according to CTCAE v5.0. Response assessments (per RECIST) occur every 8 weeks. In dose escalation, pts enter a 3-week monotherapy safety run-in of SX-682 followed by 3-week combination with nivolumab for a six-week dose-limiting toxicity (DLT) period. Cohorts 1-4 have been completed without DLT. Enrollment to cohort 5 began in January 2022. Following determination of maximum tolerated dose (MTD), dose expansion design is a Simon's optimal two-stage design. Efficacy will be assessed in the first 15 pts with a requirement of at least 2 responses in order to enroll 14 additional pts (N=29) in the second stage. Pre- and on-treatment tissue biopsies will be collected in the expansion phase. The primary objectives are to determine the safety profile of SX-682 alone and in combination with nivolumab, including the MTD, recommended phase 2 dose, and the DLT. The secondary objectives include overall response rate, progression-free survival, overall survival, and pharmacokinetic profiles of SX-682. Translational analyses include correlations of clinical outcomes with genomic and immune biomarkers from paired tissue and plasma samples. Clinical trial information: NCT04599140.
Characteristics of long-surviving patients with multiple myeloma: Over 12 years of follow-up in the Connect MM Registry.
Authors: Howard R. Terebelo, James Omel, Lynne I. Wagner, James W. Hardin, Robert M. Rifkin, Sikander Ailawadhi, Brian G. Durie, Mohit Narang, Kathleen Toomey, Cristina J. Gasparetto, Prashant Ramesh Joshi, Edward Yu, E. Dawn Flick, Weiyuan Chung, Hans C. Lee, Rafat Abonour, Sundar Jagannath
Journal: Journal of Clinical Oncology (2022)

8027 Background: The Connect MM Registry is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed multiple myeloma (NDMM) and one of the largest, longest running MM registries. Long-term survivors (LTS), defined as patients (pts) who have ≥ 8 years of follow-up, comprise a large portion of the Connect MM Registry. The purpose of this analysis was to assess LTS demographic and clinical characteristics. Methods: Adult pts with NDMM (N = 3011) were enrolled from 250 community, academic, and government sites: Cohort 1 from 2009 – 2011 and Cohort 2 from 2012 – 2016. As 99% of LTS were enrolled in Cohort 1, only pts from Cohort 1 were included in this analysis. Pt data were unevaluable if there were missing treatments, disease assessments, or large gaps in activity during follow-up (n = 28). Baseline characteristics, treatment patterns, and quality of life (QoL) form completion rates were examined. Results: At data cutoff (5/17/21), of the 1493 pts in Cohort 1 with evaluable data, 279 were LTS and 1186 were non-LTS. LTS were generally younger and had better performance status at enrollment (Table). Most (66%) LTS received stem cell transplants and few experienced progression within the first 6 months (3%). Top first-line (1L) regimen for LTS was lenalidomide/bortezomib/dexamethasone (31%) vs bortezomib/dexamethasone (22%) in non-LTS. At data cutoff, 73% of LTS were still on treatment at their most recent visit. LTS underwent disease assessments more frequently (2.0 vs 1.3 per year) and had a higher QoL completion rate by year 5 (58% vs 46%). This analysis showed an estimated 8-year survival of 36% vs an observed 8-year survival of 39% from the SEER database. Additional analyses are ongoing. Conclusions: LTS were younger and healthier than non-LTS. Most LTS received triplets at induction, stem cell transplants in 1L, and were less likely to relapse within the first 6 months of treatment than non-LTS. These findings are consistent with what has been observed in MM clinical trials. Further, this analysis demonstrates the value of longitudinal data in the CONNECT MM Registry and provides insights on long surviving pts with MM. Clinical trial information: NCT01081028. [Table: see text]
KEYNOTE B68: Open-label phase 2 study of the efficacy and safety of pembrolizumab administered every six weeks in patients with relapsed or refractory classical Hodgkin lymphoma or primary mediastinal B-cell lymphoma.
Authors: Philippe Armand, Kumudu Pathiraja, Samhita Chakraborty, Patricia Marinello
Journal: Journal of Clinical Oncology (2022)

TPS7585 Background: Classical Hodgkin lymphoma (cHL) and primary mediastinal B-cell lymphoma (PMBCL) frequently harbor amplifications at 9p24.1, leading to overexpression of PD-L1 and PD-L2, suggesting a genetically driven vulnerability to programmed death 1 (PD-1) blockade. The PD-1 inhibitor pembrolizumab, dosed at 200 mg every 3 weeks (Q3W), demonstrated strong antitumor activity and acceptable safety that led to approvals for adult and pediatric patients with relapsed or refractory (R/R) cHL and R/R PMBCL. Efficacy, safety, and pharmacokinetic (PK) results from studies in solid tumors have since led to accelerated approval for the pembrolizumab 400 mg Q6W regimen for all indications in adults; however, further efficacy and safety data are needed for hematologic indications. The open-label, single-arm, multisite, global, phase 2 KEYNOTE-B68 study (NCT04875195) evaluates the safety, efficacy, and PK profile of pembrolizumab 400 mg Q6W in patients with R/R cHL or PMBCL. Methods: Patients must have histologically confirmed R/R cHL (cohort 1) or R/R PMBCL (cohort 2) per WHO classification and radiographically measurable disease per the Lugano 2014 classification criteria and must not have previously received treatment with anti–PD-1 therapy. Eligible patients must have failed to respond to or relapsed after receiving an autologous stem cell transplant (ASCT) or must be ineligible for ASCT and must have failed to respond or relapsed after ≥1 (cHL) or ≥2 (PMBCL) prior lines of therapy; patients with PMBCL must have received ≥1 line of therapy containing rituximab. Approximately 60 patients will be enrolled. They will receive pembrolizumab 400 mg IV Q6W for up to 18 cycles. Disease assessments will occur Q12W by investigator per the Lugano 2014 response criteria. Local radiographic assessments will be collected by computed tomography Q12W and by positron emission tomography at weeks 12 and 24 and to confirm complete response. Adverse events will be monitored and assessed by investigators throughout the study, and their severity will be graded per NCI Common Terminology Criteria for Adverse Events, version 5.0 guidelines. Patients who receive an allogeneic SCT within 2 years of the last dose of study treatment will be monitored for 18 months after SCT for events of clinical interest. The primary end point (assessed per cohort) is objective response rate by investigator per the Lugano 2014 classification criteria. Secondary end points (assessed per cohort) include duration of response by investigator assessment, characterization of the PK profile and immunogenicity for pembrolizumab 400 mg Q6W, and safety. Exploratory end points assessed per cohort include overall survival, progression-free survival per the Lugano 2014 criteria, and molecular biomarker analyses. Clinical trial information: NCT04875195.